Selective removal of low density lipoprotein (LDL) by dextran sulfate affinity adsorption was evaluated in patients with familial hypercholesterolemia (FH). Patients with both homozygous and heterozygous disease were eligible for treatment as long as their plasma LDL-cholesterol concentrations exceeded 180 mg/dl despite maximal drug and dietary management. The prototype dextran sulfate apheresis system (Liposorber LA-15, Kanegafuchi, Japan) removed LDL without affecting HCL cholesterol or albumin concentrations, thus allowing return of autologous LDL-depleted plasma and avoiding the need for albumin-containing replacement solutions. One and one-half plasma volumes were processed every two weeks. Two homozygous patients completed an 18-week period of study. In these two individuals, the procedures effected a 75% reduction in total cholesterol and an 86% reduction in LDL cholesterol levels. Mean pre-procedure LDL-cholesterol levels were 237 plus/minus 31 mg/dl and post-procedure values were 34 plus/minus 4 mg/dl (n = 30). Lp(a) levels declined by 82% (47 plus/minus 27 to 8 plus/minus 4 mg/dl). HCL-cholesterol and albumin concentrations were not significantly affected by the procedures. Time-averaged LDL-cholesterol concentrations of <160 mg/dl were attained by keeping the interval between successive LDL-apheresis procedures at two weeks. The procedures were very well tolerated and no significant adverse reactions occurred. Our data suggest that dextran sulfate adsorption is a safe and effective way to selectively clear plasma of LDL-cholesterol, and has advantages, when compared to simple plasma exchange, of eliminating the need for colloid replacement solutions and promoting a more beneficial LDL-HCL cholesterol ratio.